Advancing our understanding of mycobacterial diseases, including tuberculosis and non-tuberculous mycobacterial infections, remains a global health priority. This Collection aims to highlight innovative experimental and computational approaches beyond traditional mammalian systems. There is increasing recognition that alternative models—including human relevant in vitro platforms, non-mammalian host systems, and computational frameworks—can provide mechanistic insight, improve translational relevance, and enhance experimental efficiency while addressing ethical and logistical challenges associated with animal models.

This Collection seeks to bring together interdisciplinary research spanning organoid and organ-on-a-chip technologies, zebrafish and invertebrate infection models, and in silico and systems level modeling approaches, all of which are reshaping how host-pathogen interactions, granuloma formation, persistence, and drug response are studied. By highlighting these complementary methodologies and how they might be integrated for greater impact, the Collection aims to provide a platform for showcasing next generation models that recapitulate human disease, enable high resolution mechanistic studies, and support the discovery and evaluation of new therapeutic strategies.

Submissions are encouraged from across experimental, computational, and translational disciplines, with an emphasis on approaches that either reduce or complement conventional mammalian models and contribute to a more predictive framework for mycobacterial research.

Potential topics of interest include (but are not limited to):

• Organoid and organ-on-a-chip models of mycobacterial infection
• Macrophage and airway epithelial in vitro systems
• Zebrafish and invertebrate models of mycobacterial pathogenesis
• Granuloma formation in non-mammalian or in vitro model systems
• Computational and multiscale modeling of TB infection and immunity
• Agent based and systems biology approaches to host-pathogen dynamics
• Biofilm and persistence models in non-animal systems
• High throughput and human relevant platforms for antimycobacterial drug discovery

This Collection supports and amplifies research related to SDG 3, Good Health and Well-Being.

All submissions in this collection undergo the journal’s standard peer review process. Similarly, all manuscripts authored by a Guest Editor(s) will be handled by the Editor-in-Chief. As an open access publication, this journal levies an article processing fee (details here). We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or the Editor-in-Chief.